Thionyl Chloride → 4-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride

HRID 634698ノート

反応式

HRID 634698 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:24])=O.Br[C:27]1[C:33]([OH:34])=[CH:32][C:30]([NH2:31])=[C:29]([F:35])[CH:28]=1>CN(C=O)C.C(O)(C)C.CC(C)=O>[ClH:24].[Cl:24][C:27]1[C:33]([OH:34])=[CH:32][C:30]([NH:31][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][N:7]=2)=[C:29]([F:35])[CH:28]=1

参加物

7

反応物 3

HCID 24386Thionyl ChlorideHCID 109656515-Amino-2-bromo-4-fluorophenolHCID 1354756166-Methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one

生成物 1

HCID 867563544-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride収率 83%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 180Acetone溶媒HCID 3776Isopropanol溶媒

実験手順

A mixture of 6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (260 mg, 0.90 mmol), thionyl chloride (5 ml) and DMF (2 drops) was heated at reflux for 45 minutes and allowed to cool. The excess thionyl chloride was removed by evaporation, and the residue azeotroped with toluene. A solution of 4-chloro-2-fluoro-5-hydroxyaniline (160 mg, 1.0 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) was added to the residue and the mixture was heated at reflux for 1 hour and then allowed to cool. The mixture was diluted with acetone, and the solid product collected by filtration, washed with acetone and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride(381 mg, 83%).

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 45 minutes
  3. temperatureto cool
  4. customThe excess thionyl chloride was removed by evaporation
  5. customthe residue azeotroped with toluene
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 1 hour
  8. temperatureto cool
  9. filtrationthe solid product collected by filtration
  10. washwashed with acetone
  11. customdried

出典と根拠

ORDレコード
ord-9282a78c67684690960822e4c92d5785
出典データセット
uspto-grants-2001_02
特許番号
US06184225B2

反応ノート

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